The objective of this proposal is to study the effect of alveolar carbon dioxide pressure on local blood flow in areas of low ventilation-perfusion ratio and true shunt, and, further, to determine whether or not there is interaction between hypercapnia and hypoxia in the regulation of local ventilation-perfusion relationships. The problem will be approached in three ways: 1) by determining in normal dogs and in dogs with areas of low ventilation-perfusion ratio produced by acetylcholine infusion, the effect that hypercapnia and its interaction with hypoxia has upon venous admixture, measured in the usual way, and upon ventilation-perfusion distributions measured with the inert gas technique, 2) to determine the effect that hypercapnia and its interaction with hypoxia has upon blood flow, measured with isotopically tagged microspheres, in a region of collateral ventilation produced with a double balloon catheter, 3) to perform computer modeling of the effect that hypercapnia and its interaction with hypoxia has on ventilation-perfusion distribution characterized by two or more modes, with one mode characterized by a ventilation-perfusion ratio of .1 or lower.